The present proposal is meant to meet five research aims:(1) to determine multiple developmental trajectories of substance use from early adolescence into emerging adulthood, hereby taking the co-occurrence between different types of substance use and externalising problems into account(2) to assess the outcomes of these developmental trajectories for a well defined set of individual and social parameters (the incidence of substance use disorders, neuropsychological impairment, mental health outcomes, hard drug use, educational attainment, labour market participation) in order to identify the most harmful trajectories(3) to determine the importance of underlying individual vulnerability factors (neuropsychological functioning, temperament, genetic liability) as common risk factors for the adverse developmental trajectories in order to identify the groups at risk for the most harmful trajectories (4) to analyse the moderating effect of environmental factors (ethnicity, religion, socio-economic inequality, parenting) on associations with predisctors and outcomes found for these trajectories in order to identify environmental risk factors likely to influence the most vulnerable groups. In addition, we will determine the moderating effects of gender.(5) to translate findings on risk groups and early markers into algorithms that predict problematic use, in order to support preventive practice Numerous studies have revealed that patterns of substance use in Dutch adolescents constitute important health risks. Further study into the predictors and outcomes of these patterns is therefore warranted. This proposal is meant to study developmental trajectories of substance use and addictive behaviours throughout adolescence, taking account of the strong co-occurrence with externalizing problems, hereby aiming at the following research goals: 1. to examine the developmental trajectories of substance use and externalising problems from early adolescence into young adulthood; 2. to identify the most harmful trajectories by determining the effects of these trajectories on a number of relevant psychological (substance use disorders, neurocognitive impairment, hard drug use, mental health outcomes) and social (educational attainment, labour market participation) outcomes; 3. to identify the groups at risk for developing the most adverse trajectories, while focusing on factors of individual vulnerability (genetic liability, neuropsychological impairment, temperament) as common risk factors; 4. to determine the moderating role of environmental risk factors in these processes; 5. to translate these findings into algorithms that predict problematic use to support preventive practices. These questions will be studied in a long-lasting longitudinal study, following adolescents from the age of 12 into emerging adulthood (age 20), using a large sample that is representative for the general population (n=2200).

Stress is considered to be one of the primary factors mediating the onset of depression and other affective disorders. One of the most important symptoms is the loss of motivation and interest in rewarding stimuli (anhedonia). Likely these symptoms are associated with disturbances in the dopaminergic reward system. In contrast to stress, social support has a positive effect on stress coping and the course of a depressive episode, possibly due to the rewarding effects of social contact. In my project we will therefore investigate the role of the dopaminergic reward system in the stress-reducing effects of social support. This will be done in a rat model of chronic stress/depression An important characteristic of these affective disorders is that they occur about twice as often in women. But although gender represents a critical aspect in both sensitivity to stress and psychopathology, most of the research concerning stress-related neuronal abnormalities has been conducted in males. However we will concentrate on the female gender. We thereby aim at gaining more inside in underlying mechanisms of the interaction between stress and a positive social environment in the female brain.

Background: Cognitive dysfunctions have increasingly become a focus of research in mood disorders. One-third of patients with mood disorders suffer from cognitive dysfunctions, even in a clinically asymptomatic phase (euthymia). However, due to relatively few comparative studies and many methodological pitfalls, the exact extent and kind of cognitive dysfunctions in mood disorders, as well as information about the suspected clinical and biological determinants remains unclear. Also, the relationship between cognitive dysfunctions and clinical and functional outcome parameters are understudied. More knowledge could lead to an addendum of the standard assessment in patients with mood disorders (like schizophrenic patients), and may result in new therapeutic approaches to improve quality of care, better treatment adherence and ultimately better functional outcome. Objective: The primary objective is to assess the extent and kind of cognitive dysfunctions in patients suffering from unipolar depressive mood disorders and bipolar disorders, in relation to each other and to healthy controls. Secondary objectives are to study the clinical correlates (or possible determinants) of cognitive dysfunctions (illness and patient characteristics), the biological correlate (or possible determinant) of cognitive dysfunctions (HPA axis functioning) and the (possible) consequences of cognitive dysfunctions (psychosocial functioning and illness outcome). Methods: In a cross sectional design a variety of clinical, cognitive and biological domains will be measured in 150 euthymic patients (18-65 years) with a unipolar depressive disorder (from NESDA cohort) and 150 euthymic patients (18-65 years) with a bipolar disorder (from UMC Groningen). Also, 75 healthy controls will be tested.

Aim of the formation of the creation of multifunctional units (MFUs) is the integration of the supply of care, due to which it will be possible to raise continuity and flexibility of care. This is predominantly important for long-lasting care-dependent patients. The supply of care until now scarcely has a scientific basis, since there is insufficient knowledge on the demand of care within the population. The assessment of care in this study comprises the following elements:|- The prevalence of long-lasting care-dependent patients who are not or scarcely treated by the MFU, and their realized and non-realized needs; the latter will be measured in a group (N=50) from this population;|- Need of care of long-lasting care-dependent patients who are receiving care from the MFU; this is measured in a group (N=100) from this population;|- The load of partners/relatives of these patients (N=150);|- Demand of care and satisfaction on the MFU of general practitioners and other zero and primary health care facilities.|On the basis of these elements it will be possible to evaluate the supply of care and to found it on the basis of the regional need of care.

It remains unclear whether prediction of violence based on historical factors can be improved by adding dynamic risks, protective strengths, selection of person-specific key strengths or critical vulnerabilities, and structured professional judgment (SPJ). We examine this in outpatient forensic psychiatry with the Short-Term Assessment of Risk and Treatability (START) at 3 and 6 months follow-up. An incident occurred during 33 (13%) out of 252 3-month and 44 (21%) out of 211 6-month follow-up periods (n = 188 unique clients). Pearson correlations for all predictor variables were in the expected directions. Prediction of recidivism based on historical factor ratings (odds ratio [OR] = 1.10) could not be improved through the addition of dynamic risk, protective strength, or key or critical factor scores (all ORs ns). The addition of the SPJ improved the model to modest accuracy (area under the curve [AUC] = .64) but made no independent significant contribution (OR = 1.55, p = .21) for the 3-month follow-up. For the 6-month follow-up, SPJ scores also increased predictive accuracy to modest (AUC = .67) and made a significant independent contribution to the prediction of the outcome (OR = 1.98, p = .04). Multicollinearity limits were unviolated. Limitations apply, however, results are similar to those from clinical, researcher rated samples and are discussed in the light of setting specific characteristics. Although it is too early to advocate implementing risk assessment instruments in clinical practice, we can conclude that clinicians in a heterogeneous outpatient forensic psychiatric setting can achieve similar results with the START as clinicians and research staff in more homogeneous inpatient settings.